1. Field of the Invention
The present invention relates to a point-of-care microfluidic biochip that can be used to directly perform blood typing at any place, and to a method of manufacturing the point-of-care microfluidic biochip.
2. Description of the Related Art
When a blood transfusion is necessary, blood typing for both a blood recipient and a blood donor is absolutely necessary to prevent a transfusion-caused accident. Blood typing before a blood transfusion involves performing ABO blood typing and Rh(D) blood typing, after which crossmatching is performed. Particularly, agglutinins present in serums of the ABO blood system among a variety of blood types induce hemolysis in a blood vessel by fixing unfitted red blood cells. This may result in death of a patient (blood recipient). Therefore, accurate blood typing is absolutely necessary.
Blood typing is generally performed by identifying an agglutination reaction of a red blood cell and a serum and determining that the agglutinogen corresponding to an agglutinin of the serum exists in the red blood cell. That is, when the red blood cell of a specimen reacts with an Anti-A serum to induce agglutination but does not react with an Anti-B serum, it can be determined that the red blood cell of the specimen has only agglutinogen for type-A and thus the red blood cell of the specimen can be determined as type-A. In order to perform more accurate blood typing, red cell typing (i.e., forward typing) and serum typing (i.e., backward typing) are performed. By simultaneously performing these two forms of typing, the typing results can be compared with each other and thus the reliability of the blood typing increases and a weak antigen blood type that may exist in the specimen can be detected.
Weak antigen blood types (e.g., A2, A3, Aint, and the like) exist in type-A blood and weak antigen blood types (e.g., B3, Bint, and the like) exist in type-B blood. Since the weak antigen blood types tend to be weak in agglutination reaction with the corresponding serum, the chance of mis-blood typing to type-O is high. Therefore, in order to more accurately perform blood typing, it is absolutely necessary to effectively mix red blood cells with serum. In order to improve the reliability of blood typing, it is also absolutely necessary to simultaneously perform red cell typing and serum typing.
The following conventional blood typing methods and systems are well known: plate typing, gel card typing, automatic blood typing systems, a recently represented micro-blood-typing system (S.-J. Lee, H.-W. Kang, Y. Kim, G.-W. Lee, G. Lim and D.-W. Cho, “Development of a Micro-Blood-Typing System Using Micro-Stereolithography,” Sensors and Materials, Vol. 17, pp. 113-123, 2005), and a blood typing system using a microchannel and a microfilter (Korean Patent No. 0520896).
In the case of plate typing, a specimen and a reagent are put on a plate, such as a slide glass, and mixed with each other, and after a predetermined reaction time has elapsed, it is determined if agglutination occurs. Most of the processes for plate typing are manually performed. However, due to such manual performing of the processes for plate typing, the determination of whether agglutination occurs is dependent upon a tester's subjective assessment. Thus, the typing result lacks objectivity. Further, since the specimen is manually manipulated, the tester may be at risk of infection from the specimen.
Recently, with the push toward greater automation in all aspects of diagnostic medicine, a variety of automation systems for diagnostic tests have been developed and proposed. Among these systems, the gel card typing method is known as a semiautomatic typing method that gives accurate typing results. However, the gel card typing method requires expensive supplies and testers who can manipulate a machine such as a centrifuge. In addition, since the sinking of blood takes a lot of time, the gel card typing method is time-consuming, thereby making it difficult to apply this method in an emergency.
The automatic blood typing system actually provides for fully automatic blood typing. However, the automatic blood typing system is very expensive and large in its equipment size. Hence, only large hospitals such as blood banks can utilize the automatic blood typing system.
Accordingly, Lee et al. have proposed a down-sized blood typing system in which a flow split channel, a chaos micro-mixer, and a reaction chamber are integrated through micro-stereolithography. The down-sized blood typing system splits injected blood through a flow split channel and, at the same time, mixes the blood with a reagent, after which it is determined if blood cell agglutination occurs in a reaction chamber. The down-sized blood typing system is easy to carry and may be used in dealing with emergency situations. However, a drawback of the system is that it is time-consuming to manufacture the same using the micro-stereolithography. Also, the cost of manufacturing the system is high.
Finally, all of the conventional semiautomatic or fully automatic blood typing methods need about 20 μl of the specimen for blood typing. When compared with the manual bloody typing method, there is no difference in the amount of required specimen between the manual blood typing method and the fully automatic (or semiautomatic) blood typing method. In addition, there still remains the inconvenience with respect to the need to perform repeated collection of specimens.
Korean Patent No. 0520896 discloses a blood typing system using a microchannel and a microfilter. This blood typing system uses a method in which a specimen is split through the microchannel and reacts with a reagent in a reagent storing chamber, and agglutinated blood is filtered off through the microfilter. Further, this blood typing system uses a relatively small amount (10 μl or less) of the specimen. However, this blood typing system is configured to induce natural mixing and reaction between the specimen and the reagent in the micro-chamber. As described above, effective mixing of the specimen and the reagent is essential in order to detect an unexpected antibody that may exist in the blood cell. With the use of such a fine channel or micro channel, however, only a mixing effect by diffusion can be expected due to a reduction in a characteristic length, while a mixing effect by turbulence cannot be expected. Therefore, mixing performance is significantly deteriorated. For example, several hours are necessary for the natural mixture by diffusion in a microchannel having a width of 100 μm. Therefore, the micro blood typing system not having a mixing apparatus is limited in performance. Furthermore, in this blood typing system, the microfilter is formed in a cylindrical shape having a uniform thickness in a lengthwise direction. However, the thickness of the microfilter is too small to be mass-produced through, for example, an injection molding process. Finally, the blood typing system disclosed in Korean Patent No. 0520896 uses specific, preset reagents and is designed to perform a blood cell test. Thus, this blood typing system has limitations with respect to accurately performing blood typing.
Therefore, there is a need to develop an agglutination test system for diagnostic medicine, that, in a single apparatus, can perform a reaction between a specimen and a reagent and read if agglutination occurs while using a relatively small amount of each of the specimen and the reagent, thereby enabling (i) an objective diagnosis of the agglutination test for blood typing, (ii) preservation of the agglutination test result, (iii) cheap manufacture, and (iv) point-of-care resulting from easy portability.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.